Ulcerative colitis is an inflammatory disease of the large intestine that causes erosions and/or ulcers in the mucosa of the large intestine, and classified into mild, moderate, severe, and fulminant diseases according to the severity. Main symptoms of ulcerative colitis include diarrhea and bloody stool. In addition, ulcerative colitis often repeats an active stage during which the above symptoms appear, and a remission stage during which the above symptoms subside by a treatment.
A treatment guideline against ulcerative colitis recommends that an appropriate drug should be selected depending on the severity and the symptom of the disease, but the treatment is mainly given with a 5-aminosalicylic acid preparation (also referred to as 5-ASA preparation) and a corticosteroid preparation. In the standard treatment, an oral 5-ASA preparation is used alone or in combination with a topical preparation. Nevertheless, if the effect is insufficient, the remission is induced by a treatment with an oral corticosteroid preparation. A patient recognized as having resistance to or dependency on the corticosteroid preparation treatment is considered as a refractory case. For the treatment of such patients, apheresis, tacrolimus oral administration, azathioprine or 6-mercaptopurine (6-MP), or an anti-TNFα antibody preparation is selected (Non Patent Literature 1).
A 5-ASA preparation occasionally causes an allergic reaction with fever and diarrhea. For patients who cannot receive the standard treatment from the above reasons, there is a great need for a novel treatment option. Meanwhile, a corticosteroid preparation can be expected to exhibit a strong efficacy, but is well known to have a side-effect problem such as infectious diseases. The risk of infectious diseases from a 5-ASA preparation is at the same level as in the non-treatment, whereas a corticosteroid preparation has been reported to increase the risk by 3.3 fold. Furthermore, various side effects thereof are known such as hyperglycemia, adrenal gland disorder, and osteoporosis.
Additionally, since the apheresis is an extracorporeal circulation procedure, this puts a physically heavy burden and a long restraint on a patient. The tacrolimus oral administration has been reported to have serious side effects such as renal dysfunction and pancreatic dysfunction, so that a complicated trough level control is necessary through hospitalization or under a control comparable to the hospitalization. Hence, the tacrolimus oral administration is disadvantageous in that the burdens of the subject and medical staff are considerable even though the drug is an oral preparation. Infliximab intravenous infusion is known to cause antigenic infusion reaction and delayed type hypersensitivity in addition to a lethal side effect such as hepatosplenic T-cell lymphoma, one of malignant tumors. Moreover, there is a report that, among the administered patients, at most approximately 70% of the patients showed the loss of the response. A secondary failure is one of causes of the loss, and is a major problem (Non Patent Literatures 2 to 6).